- Email: [email protected]
Parathyroid Insufficiency
Medical Clinics of North America July, 1940. Mayo Clinic Number
. PARATHYROID INSUFFICIENCY SAMUEL
F.
HAINES
Parathyroid insufficiency is predominantly a disease of women; it rarely affects men. It may follow surgical operations on the thyroid gland, operations directly on the parathyroid glands, or, in rare instances, may occur spontaneously. Following partial thyroidectomy for goiter, hypoparathyroidism occurs in about 0.05 per cent of cases. 5 It may result from the inadvertent removal of parathyroid glands due to abnormal situation of the glands 1iO or possibly from disturbances in circulation or other mechanical interference which may accompany or follow the operation. It is also possible that parathyroid insufficiency may result from inflammatory changes in the parathyroid glands, for rarely instances have been observed of parathyroid insufficiency following late after partial thyroidectomy for microscopically proved thyroiditis. In such cases, myxedema has also occurred. Parathyroid insufficiency naturally has been reported with greater frequency following total thyroidectomy performed because of heart disease, than following partial thyroidectomy for various types of go iter. Temporary, and frequently severe, parathyroid insufficiency often follows the surgical removal of parathyroid tumors from patients who have hyperparathyroidism. In such case, the parathyroid glands that are not involved in the tumor are probably put at rest by the presence in the body of excessive parathyroid hormone. Spontaneous parathyroid insufficiency is very rare. The reported cases have been recognized, in many instances, because of. accompanying disturbances; for example, cataract, convulsions, symmetrical cerebral calcification and so forth. The insufficiency in such cases is usually severe and usually is of long duration. 101 9
1020
SAMUEL F. HAINES SYMPTOMS AND SIGNS
Acute parathyroid insufliciency.-When parathyroid insufficiency follows operations on the thyroid or parathyroid gland, symptoms and signs may occur within twenty-four hours of the operation. The order of onset of symptoms is not consistent and in fact, symptoms may not be mentioned by the patient. Numbness of the face and hands is the most frequently noted symptom. Carpopedal spasm may occur before the numbness is mentioned or noticed. Difficulty in visual accommodation may be an early symptom that may exist for several days before numbness occurs. Laryngeal spasm, a condition which rarely occurs in this condition unless one vocal cord is paralyzed, may be an early and distressing symptom. Because of the seriousness of this symptom, such a condition occurring after thyroidectomy had best be assumed to be due to parathyroid insufficiency and appropriate treatment should be instituted. Chvostek's sign is almost always positive in cases of acute parathyroid insufficiency. Unfortunately, it is also occasionally positive in an otherwise normal individual, so that its presence is not pathognomonic. Trousseau's sign is slower in becoming positive than is Chvostek's but it is of more significance when positive. However, one must use caution in its interpretation, as I have seen patients with positive Trousseau's signs whose concentration of calcium and phosphorus in the blood was normal and for whom vigorous treatment for parathyroid insufficiency produced no effect on the sign. In this regard, it should be noted that the signs of parathyroid insufficiency have been ably mimicked by some hypersensitive and apprehensive patients. Chronic parathyroid insufticiencY.-In some instances, the symptoms of parathyroid insufficiency are so mild as to be overlooked completely. In such cases, if the condition persists, recognition may be difficult because of the absence of tetany. Fatigue and muscular weakness, gastro-intestinal irritability and trophic disturbances such as marked disturbances in growth of the nails may be encountered. One of the most serious of the disturbances that occur in cases of chronic parathyroid tetany is cataract. Recently, a few cases of symmetrical regions of calcification in the brain have been described in association
PARATHYROID INSUFFICIENCY
1021
with untreated chronic parathyroid insufficiency.6 Mental retardation may occur. As in cases of acute tetany, if one vocal cord is paralyzed, frequent and prolonged attacks of laryngeal spasm may occur. During such attacks, respiratory stridor is severe; the vocal cords have been seen to be very close together in one such case. 7 It is doubtful that such a condition is common. Generalized convulsions are seen occasionally in severe cases of parathyroid insufficiency. Such convulsions are often preceded by typical carpopedal spasm and this may be considered a diagnostic point. Convulsions have not occurred in our cases following control of the insufficiency. The signs and symptoms of parathyroid insufficiency may occur either in the presence of a low concentration of calcium in the blood and an increase in the inorganic phosphates of the blood or during a period when the concentration of the blood calcium is falling and that of the inorganic phosphates is rising. Ordinarily, in acute cases following thyroidectomy, the concentration of blood calcium will be less than 7 mg. per 100 c.c. and that of the inorganic phosphates greater than 2.5 to 3 mg. per 100 c.c. In chronic cases, blood calcium levels of less than 7 mg. per 100 c.c. are expected. In the same way, inorganic phosphate in the blood occasionally rises to 5 or 6 mg. per 100 c.c. It is important to remember that during a period of falling blood calcium and rising blood phosphorus, the signs and symptoms of the disease may occur even though the actual chemical levels are within the usual normal limits. This situation may exist following the removal of a parathyroid tumor for hyperparathyroidism when the blood calcium is decreasing from its customarily increased level to the normal level. The level of magnesium in the blood is reduced in cases of parathyroid insufficiency but, at present, the determination of this element is not considered of importance in recognition or treatment of the condition, nor are studies of ionized and unionized calcium essential to the successful diagnosis and management of the disease. DIFFERENTIAL DIAGNOSIS
Not all patients who present evidences of tetany are suffering from hypoparathyroidism. Tetany associated with hyperventilation is usually easily recognized when the patient is seen
1022
SAMUEL F. HAINES
in an attack. When the patient's description is obtained and no attack has been witnessed by the physician, hyperventilation tetany may occasionally be misdiagnosed as parathyroid insufficiency. This difficulty should not occur as in the former condition, Trousseau's sign is not usually positive between attacks, or at least unless some degree of hyperventilation exists. The blood calcium and phosphorus are normal. Tetany associated with loss of chlorides due to excessive vomiting is rarely confused with that caused by parathyroid insufficiency. In the case of tetany due to loss of chlorides in vomitus, again, the history is quite different from that associated with parathyroid insufficiency and the results of chemical examinations in the former are entirely different from those in the latter condition. In cases of tetany from excessive vomiting, the concentration of blood chlorides is lowered and that of blood urea is usually elevated; the calcium and phosphorus are normal. Marked numbness of the extremities that persists after adequate treatment in a case of parathyroid insufficiency should always call to mind the possibility of the existence of myxedema, in which condition such a complaint is often heard. A variable degree of myxedema occasionally accompanies parathyroid insufficiency, and of course both conditions must be recognized and be adequately treated to obtain a satisfactory result. TREATMENT
Calcium.-The treatment of acute parathyroid insufficiency consists essentially in the administration of large doses of calcium. When sufficient urgency exists, calcium may be given intravenously in the form of 10 C.c. of a 10 per cent solution of calcium chloride or of calcium gluconate. The latter, although it contains relatively less calcium than the calcium chloride and must, therefore, be used in larger amounts, ~s the important advantage of being much less irritating than calcium chloride if small amounts should be deposited outside the vein. Necrosis may follow the inadvertent injection of small quantities of calcium chloride into subcutaneous tissues. In most cases, calcium can be given orally. It may be necessary to give large doses frequently, and when calcium lactate is used, it must be dissolved in very hot water, as relatively
PARATHYROID INSUFFICIENCY
102 3
little is absorbed if it is merely mixed with cold water. The lactate given in 2 to 5 gm. doses every fifteen to thirty minutes is usually the most satisfactory therapeutic agent in acute cases. After control has been achieved, maintenance doses vary from 2 to 4 gm. three or four times daily up to 10 gm. four or five times da,ily. It has been reported that large doses of calcium salts are not well tolerated by many patients. We have found this to be true only in occasional instances. In some, diarrhea has followed daily doses of 50 gm. or more of calcium lactate, and in some, na,usea has occurred. In some cases in which diarrhea has developed, achlorhydria has been found and in these cases and in some of those in which the gastric contents were not examined, the administration of dilute hydrochloric acid has been followed by cessation of diarrhea. In conjunction with calcium some form of vitamin D is essential for adequate treatment. This is true because vitamin D increases the absorption of calcium from the intestine and if vitamin D is not used, many patients will fail to derive from absorption enough calcium to bring the concentration of calcium in the serum to sufficiently high levels to control symptoms of the disease. Boothby 4 has reported progression of cataracts in a case in which adequate amounts of calcium were given but in which vitamin D was not administered. For practical purposes cod liver oil is very satisfactory, although some patients object to it. They may be given anyone of the multitude of preparations that contain adequate amounts of vitamin D. It is possibly true that large doses of vitamin D, such as 25,000 units daily, may enable control of the disease with smaller doses of calcium, but the difference in effect with increasing doses of vitamin D is by no means quantitative and it is desirable to keep the dose of vitamin D low enough to prevent the development of hypercalcemia. Experimentally, very large doses of crystalline vitamin D have been used to control parathyroid insufficiency without the addition of large amounts of calcium, bp.t from a practical standpoint the condition may be readily and cheaply treated by the aforementioned means. In chronic severe cases, reduction of phosphorus in the diet somewhat increases the ease of control, but this, too, is frequently unnecessary .
1024
SAMUEL F. RAINES
Dihydrotachysterol (A. T. 10).-In 1934, Holtz, Gissel and Rossman introduced a new drug, dihydrotachysterol (A. T. 10) (Antitetanisches Praparat. Nr. 10) in the treatment of this disease, and subsequently Arnold and Blum, Albright,2 MacBryde, and others have described its use in large series of cases. This drug, a fraction of irradiated ergosterol, has the power of increasing the absorption of calcium and of greatly increasing the excretion of phosphorus and acts, therefore, more like the parathyroid hormone than does vitamin D. Used in small doses, such as 2 to 5 c.c. weekly, it makes large doses of calcium unnecessary and offers the easiest and most pleasant method of treatment yet devised. Ordinarily, even with dihydrotachysterol, some calcium should be given and doses of 6 teaspoonfuls of calcium gluconate daily can be' taken easily and will make the requirement of dihydrotachysterol (A. T. 10) much less than when no added calcium is taken. Caution must be observed in the use of this drug, as marked elevation of the blood calcium may occur in short periods of time and metastatic calcification and skeletal decalcification have occurred following its experimental use in animals. The individual dose must be ascertained by trial and observation over a period of several weeks or months before it can be contin~ed with safety. Para.thyroid hormone.-The parathyroid hormone had a more important place in treatment in the past than it has since dihydrotachysterol has been made available. At present, the greatest usefulness of the parathyroid hormone is for patients who are acutely ill and are unable to take sufficient doses of calcium orally. Patients who have chronic severe parathyroid insufficiency for whom surgical operations are performed may be treated easily during the first few postoperative days by administration of parathyroid hormone, the usual treatment with calcium and vitamin D or A. T. 10 being resumed after the patient is able to take them orally. For pro~ longed treatment, even the most severe cases can be controlled readily without use of the hormone. Guides to treatment.-The most satisfactory guide in treatment is the chemical examination of the blood. Ordinarily, if blood calcium levels of 8.5 to 9.5 mg. per 100 c.c. can be maintained, treatment may be considered satisfactory. Cer-
PARATHYROID INSUFFICIENCY
102 5
tainly it is not necessary to hold the concentration of calcium in the blood to 10 mg. per 100 C.c. to keep the patient free of symptoms and it is undesirable to hold the calcium at levels higher than 10 mg. per 100 c.c. Recently, Albright1 has described a criterion for treatment in which the urinary excretion of calcium is used as a guide; the dosage of dihydrotachysterol is reduced when large amounts of calcium appear in the urine and is increased when the urine is free of calcium. Whatever method of treatment is used, control of parathyroid insufficiency can and should be complete and constant. . When such control is maintained, the patient, if otherwise well, should maintain normal health and be entirely free from the development of any of the secondary or late disturbances that occur so frequently in chronic cases of long duration. Treatment of the condition should be constant, not intermittent, and it is important that, from the start, the patient with chronic parathyroid insufficiency should be aware of the importance of continuous treatment. When convulsions have been present they have entirely ceased after treatment. This has been true even in those cases in which symmetrical cerebral calcification is present, in which the latter condition has, of course, remained unchanged. Thus, it appears certain that the convulsions are not dependent on the cerebral calcification. Convulsions have, in fact, been encountered in many cases in which cerebral calcification could not be demonstrated. The progress of cataracts that result from parathyroid insufficiency is frequently stopped by treatment, although in rare cases progress has continued. Indeed, slight improvement in cataracts has been reported in very rare instances, but it is not certain that the improvement has been great or persistent. Trophic disturbances usually disappear with comparative rapidity. The usual symptoms and such disturbances as laryngeal spasm, difficulty in focusing the eyes and so forth should disappear within a few hours after the institution of adequate treatment. Definite improvement in the mental status has been observed within a few weeks. In many mild cases, it has been possible to discontinue treatment or to reduce it greatly after months or even years and to have no clinical or chemical evidences of recurrence. Patients who have such a condition, however, should be under observation for long periods of time VOL. 24-65
1026
SAMUEL F. IIAINES
before being allowed to go free of treatment, as periods of unusual stress such as infection, pregnancy and lactation may be accompanied by recurrence of the disease. BIBLIOGRAPHY 1. Albright, Fuller: Note on the management of hypoparathyroidism with dihydrotachysterol. J .A.M.A., 112: 2592-2593 (] une 24) 1939.
2. Albright, Fuller, Bloomberg, Esther, Drake, Truman and Sulkowitch, H. W.: A comparison of the effects of A.T. 10 (dihYdrotachysterol) and vitamin D on calcium and phosphorus metabolism in hypoparathyroidism. ] our. Clin. Investigation, 17: 317-329 (May) 1938. 3. Arnold, C. H. and Blum, H.: Control of hypoparathyroidism. West. ]. Surg., ,,: 546-555 (Sept.) 1936. 4. Boothby, W. M. and Lillie, W. J.: A case of parathyroid insufficiency. Proc. Staff Meet., Mayo Clin., 7: 361-362 (June 22) 1932. 5. Boothby, W. M., Haines, S. F. and Pemberton, ]. de].: Postoperative \ parathyroid insufficiency. Am. J. M. Se., 181: 81-96 (Jan. 1) 1931. 6. Eaton, L. M. and Haines, S. F.: Parathyroid insufficiency with symmetrical cerebral calcification, report of 3 cases, in one of which the patient was treated with dihydrotachysterol. J.A.M.A., 113: 749-753 (Aug. 26) 1939. 7. Figi, F. A.: Personal communication to the author. 8. Holtz, F., Gissel, H. and Rossmann, E.: Experimentelle und klinische Studien zur Behandlung der postoperativen Tetanie mit A.T. 10. Deutsche Ztschr. f. Chir., 242: 521-569 (Mar.) 1934. 9. MacBryde, C. M.: The treatment of parathyroid tetany with dihydrotachysterol. J.A.M.A., 111: 304-307 (July 23) 1938. 10. Searls, H. H.: Parathyroid protection. Tr. Am. A. Study Goiter, 7: 191-193 (Aug.) 1929.
. PARATHYROID INSUFFICIENCY SAMUEL
F.
HAINES
Parathyroid insufficiency is predominantly a disease of women; it rarely affects men. It may follow surgical operations on the thyroid gland, operations directly on the parathyroid glands, or, in rare instances, may occur spontaneously. Following partial thyroidectomy for goiter, hypoparathyroidism occurs in about 0.05 per cent of cases. 5 It may result from the inadvertent removal of parathyroid glands due to abnormal situation of the glands 1iO or possibly from disturbances in circulation or other mechanical interference which may accompany or follow the operation. It is also possible that parathyroid insufficiency may result from inflammatory changes in the parathyroid glands, for rarely instances have been observed of parathyroid insufficiency following late after partial thyroidectomy for microscopically proved thyroiditis. In such cases, myxedema has also occurred. Parathyroid insufficiency naturally has been reported with greater frequency following total thyroidectomy performed because of heart disease, than following partial thyroidectomy for various types of go iter. Temporary, and frequently severe, parathyroid insufficiency often follows the surgical removal of parathyroid tumors from patients who have hyperparathyroidism. In such case, the parathyroid glands that are not involved in the tumor are probably put at rest by the presence in the body of excessive parathyroid hormone. Spontaneous parathyroid insufficiency is very rare. The reported cases have been recognized, in many instances, because of. accompanying disturbances; for example, cataract, convulsions, symmetrical cerebral calcification and so forth. The insufficiency in such cases is usually severe and usually is of long duration. 101 9
1020
SAMUEL F. HAINES SYMPTOMS AND SIGNS
Acute parathyroid insufliciency.-When parathyroid insufficiency follows operations on the thyroid or parathyroid gland, symptoms and signs may occur within twenty-four hours of the operation. The order of onset of symptoms is not consistent and in fact, symptoms may not be mentioned by the patient. Numbness of the face and hands is the most frequently noted symptom. Carpopedal spasm may occur before the numbness is mentioned or noticed. Difficulty in visual accommodation may be an early symptom that may exist for several days before numbness occurs. Laryngeal spasm, a condition which rarely occurs in this condition unless one vocal cord is paralyzed, may be an early and distressing symptom. Because of the seriousness of this symptom, such a condition occurring after thyroidectomy had best be assumed to be due to parathyroid insufficiency and appropriate treatment should be instituted. Chvostek's sign is almost always positive in cases of acute parathyroid insufficiency. Unfortunately, it is also occasionally positive in an otherwise normal individual, so that its presence is not pathognomonic. Trousseau's sign is slower in becoming positive than is Chvostek's but it is of more significance when positive. However, one must use caution in its interpretation, as I have seen patients with positive Trousseau's signs whose concentration of calcium and phosphorus in the blood was normal and for whom vigorous treatment for parathyroid insufficiency produced no effect on the sign. In this regard, it should be noted that the signs of parathyroid insufficiency have been ably mimicked by some hypersensitive and apprehensive patients. Chronic parathyroid insufticiencY.-In some instances, the symptoms of parathyroid insufficiency are so mild as to be overlooked completely. In such cases, if the condition persists, recognition may be difficult because of the absence of tetany. Fatigue and muscular weakness, gastro-intestinal irritability and trophic disturbances such as marked disturbances in growth of the nails may be encountered. One of the most serious of the disturbances that occur in cases of chronic parathyroid tetany is cataract. Recently, a few cases of symmetrical regions of calcification in the brain have been described in association
PARATHYROID INSUFFICIENCY
1021
with untreated chronic parathyroid insufficiency.6 Mental retardation may occur. As in cases of acute tetany, if one vocal cord is paralyzed, frequent and prolonged attacks of laryngeal spasm may occur. During such attacks, respiratory stridor is severe; the vocal cords have been seen to be very close together in one such case. 7 It is doubtful that such a condition is common. Generalized convulsions are seen occasionally in severe cases of parathyroid insufficiency. Such convulsions are often preceded by typical carpopedal spasm and this may be considered a diagnostic point. Convulsions have not occurred in our cases following control of the insufficiency. The signs and symptoms of parathyroid insufficiency may occur either in the presence of a low concentration of calcium in the blood and an increase in the inorganic phosphates of the blood or during a period when the concentration of the blood calcium is falling and that of the inorganic phosphates is rising. Ordinarily, in acute cases following thyroidectomy, the concentration of blood calcium will be less than 7 mg. per 100 c.c. and that of the inorganic phosphates greater than 2.5 to 3 mg. per 100 c.c. In chronic cases, blood calcium levels of less than 7 mg. per 100 c.c. are expected. In the same way, inorganic phosphate in the blood occasionally rises to 5 or 6 mg. per 100 c.c. It is important to remember that during a period of falling blood calcium and rising blood phosphorus, the signs and symptoms of the disease may occur even though the actual chemical levels are within the usual normal limits. This situation may exist following the removal of a parathyroid tumor for hyperparathyroidism when the blood calcium is decreasing from its customarily increased level to the normal level. The level of magnesium in the blood is reduced in cases of parathyroid insufficiency but, at present, the determination of this element is not considered of importance in recognition or treatment of the condition, nor are studies of ionized and unionized calcium essential to the successful diagnosis and management of the disease. DIFFERENTIAL DIAGNOSIS
Not all patients who present evidences of tetany are suffering from hypoparathyroidism. Tetany associated with hyperventilation is usually easily recognized when the patient is seen
1022
SAMUEL F. HAINES
in an attack. When the patient's description is obtained and no attack has been witnessed by the physician, hyperventilation tetany may occasionally be misdiagnosed as parathyroid insufficiency. This difficulty should not occur as in the former condition, Trousseau's sign is not usually positive between attacks, or at least unless some degree of hyperventilation exists. The blood calcium and phosphorus are normal. Tetany associated with loss of chlorides due to excessive vomiting is rarely confused with that caused by parathyroid insufficiency. In the case of tetany due to loss of chlorides in vomitus, again, the history is quite different from that associated with parathyroid insufficiency and the results of chemical examinations in the former are entirely different from those in the latter condition. In cases of tetany from excessive vomiting, the concentration of blood chlorides is lowered and that of blood urea is usually elevated; the calcium and phosphorus are normal. Marked numbness of the extremities that persists after adequate treatment in a case of parathyroid insufficiency should always call to mind the possibility of the existence of myxedema, in which condition such a complaint is often heard. A variable degree of myxedema occasionally accompanies parathyroid insufficiency, and of course both conditions must be recognized and be adequately treated to obtain a satisfactory result. TREATMENT
Calcium.-The treatment of acute parathyroid insufficiency consists essentially in the administration of large doses of calcium. When sufficient urgency exists, calcium may be given intravenously in the form of 10 C.c. of a 10 per cent solution of calcium chloride or of calcium gluconate. The latter, although it contains relatively less calcium than the calcium chloride and must, therefore, be used in larger amounts, ~s the important advantage of being much less irritating than calcium chloride if small amounts should be deposited outside the vein. Necrosis may follow the inadvertent injection of small quantities of calcium chloride into subcutaneous tissues. In most cases, calcium can be given orally. It may be necessary to give large doses frequently, and when calcium lactate is used, it must be dissolved in very hot water, as relatively
PARATHYROID INSUFFICIENCY
102 3
little is absorbed if it is merely mixed with cold water. The lactate given in 2 to 5 gm. doses every fifteen to thirty minutes is usually the most satisfactory therapeutic agent in acute cases. After control has been achieved, maintenance doses vary from 2 to 4 gm. three or four times daily up to 10 gm. four or five times da,ily. It has been reported that large doses of calcium salts are not well tolerated by many patients. We have found this to be true only in occasional instances. In some, diarrhea has followed daily doses of 50 gm. or more of calcium lactate, and in some, na,usea has occurred. In some cases in which diarrhea has developed, achlorhydria has been found and in these cases and in some of those in which the gastric contents were not examined, the administration of dilute hydrochloric acid has been followed by cessation of diarrhea. In conjunction with calcium some form of vitamin D is essential for adequate treatment. This is true because vitamin D increases the absorption of calcium from the intestine and if vitamin D is not used, many patients will fail to derive from absorption enough calcium to bring the concentration of calcium in the serum to sufficiently high levels to control symptoms of the disease. Boothby 4 has reported progression of cataracts in a case in which adequate amounts of calcium were given but in which vitamin D was not administered. For practical purposes cod liver oil is very satisfactory, although some patients object to it. They may be given anyone of the multitude of preparations that contain adequate amounts of vitamin D. It is possibly true that large doses of vitamin D, such as 25,000 units daily, may enable control of the disease with smaller doses of calcium, but the difference in effect with increasing doses of vitamin D is by no means quantitative and it is desirable to keep the dose of vitamin D low enough to prevent the development of hypercalcemia. Experimentally, very large doses of crystalline vitamin D have been used to control parathyroid insufficiency without the addition of large amounts of calcium, bp.t from a practical standpoint the condition may be readily and cheaply treated by the aforementioned means. In chronic severe cases, reduction of phosphorus in the diet somewhat increases the ease of control, but this, too, is frequently unnecessary .
1024
SAMUEL F. RAINES
Dihydrotachysterol (A. T. 10).-In 1934, Holtz, Gissel and Rossman introduced a new drug, dihydrotachysterol (A. T. 10) (Antitetanisches Praparat. Nr. 10) in the treatment of this disease, and subsequently Arnold and Blum, Albright,2 MacBryde, and others have described its use in large series of cases. This drug, a fraction of irradiated ergosterol, has the power of increasing the absorption of calcium and of greatly increasing the excretion of phosphorus and acts, therefore, more like the parathyroid hormone than does vitamin D. Used in small doses, such as 2 to 5 c.c. weekly, it makes large doses of calcium unnecessary and offers the easiest and most pleasant method of treatment yet devised. Ordinarily, even with dihydrotachysterol, some calcium should be given and doses of 6 teaspoonfuls of calcium gluconate daily can be' taken easily and will make the requirement of dihydrotachysterol (A. T. 10) much less than when no added calcium is taken. Caution must be observed in the use of this drug, as marked elevation of the blood calcium may occur in short periods of time and metastatic calcification and skeletal decalcification have occurred following its experimental use in animals. The individual dose must be ascertained by trial and observation over a period of several weeks or months before it can be contin~ed with safety. Para.thyroid hormone.-The parathyroid hormone had a more important place in treatment in the past than it has since dihydrotachysterol has been made available. At present, the greatest usefulness of the parathyroid hormone is for patients who are acutely ill and are unable to take sufficient doses of calcium orally. Patients who have chronic severe parathyroid insufficiency for whom surgical operations are performed may be treated easily during the first few postoperative days by administration of parathyroid hormone, the usual treatment with calcium and vitamin D or A. T. 10 being resumed after the patient is able to take them orally. For pro~ longed treatment, even the most severe cases can be controlled readily without use of the hormone. Guides to treatment.-The most satisfactory guide in treatment is the chemical examination of the blood. Ordinarily, if blood calcium levels of 8.5 to 9.5 mg. per 100 c.c. can be maintained, treatment may be considered satisfactory. Cer-
PARATHYROID INSUFFICIENCY
102 5
tainly it is not necessary to hold the concentration of calcium in the blood to 10 mg. per 100 C.c. to keep the patient free of symptoms and it is undesirable to hold the calcium at levels higher than 10 mg. per 100 c.c. Recently, Albright1 has described a criterion for treatment in which the urinary excretion of calcium is used as a guide; the dosage of dihydrotachysterol is reduced when large amounts of calcium appear in the urine and is increased when the urine is free of calcium. Whatever method of treatment is used, control of parathyroid insufficiency can and should be complete and constant. . When such control is maintained, the patient, if otherwise well, should maintain normal health and be entirely free from the development of any of the secondary or late disturbances that occur so frequently in chronic cases of long duration. Treatment of the condition should be constant, not intermittent, and it is important that, from the start, the patient with chronic parathyroid insufficiency should be aware of the importance of continuous treatment. When convulsions have been present they have entirely ceased after treatment. This has been true even in those cases in which symmetrical cerebral calcification is present, in which the latter condition has, of course, remained unchanged. Thus, it appears certain that the convulsions are not dependent on the cerebral calcification. Convulsions have, in fact, been encountered in many cases in which cerebral calcification could not be demonstrated. The progress of cataracts that result from parathyroid insufficiency is frequently stopped by treatment, although in rare cases progress has continued. Indeed, slight improvement in cataracts has been reported in very rare instances, but it is not certain that the improvement has been great or persistent. Trophic disturbances usually disappear with comparative rapidity. The usual symptoms and such disturbances as laryngeal spasm, difficulty in focusing the eyes and so forth should disappear within a few hours after the institution of adequate treatment. Definite improvement in the mental status has been observed within a few weeks. In many mild cases, it has been possible to discontinue treatment or to reduce it greatly after months or even years and to have no clinical or chemical evidences of recurrence. Patients who have such a condition, however, should be under observation for long periods of time VOL. 24-65
1026
SAMUEL F. IIAINES
before being allowed to go free of treatment, as periods of unusual stress such as infection, pregnancy and lactation may be accompanied by recurrence of the disease. BIBLIOGRAPHY 1. Albright, Fuller: Note on the management of hypoparathyroidism with dihydrotachysterol. J .A.M.A., 112: 2592-2593 (] une 24) 1939.
2. Albright, Fuller, Bloomberg, Esther, Drake, Truman and Sulkowitch, H. W.: A comparison of the effects of A.T. 10 (dihYdrotachysterol) and vitamin D on calcium and phosphorus metabolism in hypoparathyroidism. ] our. Clin. Investigation, 17: 317-329 (May) 1938. 3. Arnold, C. H. and Blum, H.: Control of hypoparathyroidism. West. ]. Surg., ,,: 546-555 (Sept.) 1936. 4. Boothby, W. M. and Lillie, W. J.: A case of parathyroid insufficiency. Proc. Staff Meet., Mayo Clin., 7: 361-362 (June 22) 1932. 5. Boothby, W. M., Haines, S. F. and Pemberton, ]. de].: Postoperative \ parathyroid insufficiency. Am. J. M. Se., 181: 81-96 (Jan. 1) 1931. 6. Eaton, L. M. and Haines, S. F.: Parathyroid insufficiency with symmetrical cerebral calcification, report of 3 cases, in one of which the patient was treated with dihydrotachysterol. J.A.M.A., 113: 749-753 (Aug. 26) 1939. 7. Figi, F. A.: Personal communication to the author. 8. Holtz, F., Gissel, H. and Rossmann, E.: Experimentelle und klinische Studien zur Behandlung der postoperativen Tetanie mit A.T. 10. Deutsche Ztschr. f. Chir., 242: 521-569 (Mar.) 1934. 9. MacBryde, C. M.: The treatment of parathyroid tetany with dihydrotachysterol. J.A.M.A., 111: 304-307 (July 23) 1938. 10. Searls, H. H.: Parathyroid protection. Tr. Am. A. Study Goiter, 7: 191-193 (Aug.) 1929.